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A Semiconductor DNA Sequencer

Unlike other systems, Ion Torrent’s technology promises to improve in step with advances in electronics—and it’s already proving useful for public health.

Last December, Ion Torrent, something of an upstart in the sequencing industry, launched its new semiconductor-based sequencing machine. At $50,000, it was a comparatively inexpensive device designed to move DNA sequencing from large, specialized centers to the standard lab bench. Now the company says its machine is en route to becoming the most popular one in a competitive market.

Speed sequence: Ion Torrent’s semiconductor chip (shown here) can sequence samples of DNA in just a few hours.

Life Technologies, which bought Ion Torrent for $375 million in cash and stock last August, is feeling good about its bet. The technology has already proved its worth as a valuable public health tool. In June, two different groups used the Ion Torrent machine to rapidly sequence the genome of a new strain of E. coli that killed more than 20 people in Europe. The effort helped identify the microbe’s drug-resistance genes. And researchers across the globe are using it to sequence genes involved in cancer and other diseases, with the aim of creating rapid tests to determine the best medicine for a patient.

Ion Torrent is competing with a number of sequencing technologies, all racing to become the fastest and cheapest: a landmark goal in the field is to sequence an entire human genome for $1,000, which would put it on par with many other routine medical tests. But Jonathan Rothberg, Ion Torrent’s founder, says his technology, which is based on semiconductors, is getting better faster than anyone else’s.

Most advanced sequencing technologies rely on fluorescently tagged molecules and a microscope to sequence DNA. At the heart of Ion Torrent’s machine are sequencing chips that detect DNA sequences electronically. This approach removes the need for expensive lasers and cameras. The chips are made in the same semiconductor fabs as computer microprocessors. And just as with computer chips, production costs per chip drop as larger numbers are produced. As sales of the Ion Torrent machine have risen, the cost of the sequencing chips has dropped from $250 to $99.

Researchers have also improved the chip’s sequencing capacity by tenfold; each chip can generate 100 million base pairs, up from 10 million base pairs when the technology first launched. Rothberg says a third-generation chip capable of sequencing a billion bases will be available next year.

As a tip of the hat to the power of superconductors, Ion Torrent has now sequenced the full genome of Intel cofounder Gordon E. Moore, now 82. Moore is best known as the creator of Moore’s law, which posits that the processing power of new chips would double approximately every two years. Ion Torrent’s chip has improved tenfold over six months, a rapid advance that Rothberg attributes to “accumulated Moore’s law,” or the decades of research and billions of dollars that have gone into making faster microprocessors.

At this point, Ion Torrent’s technology isn’t well-suited to sequencing entire human genomes. Moore’s sequence required about 1,000 chips and a total cost of about $200,000. Other technologies, in contrast, have brought the cost of a whole genome down to $5,000 to $20,000, depending on how the cost is calculated.

Ion Torrent’s technology is most adept at sequencing small genomes, like those of microbes, or a selection of genes, such as those that have been linked to cancer. “We are not the cheapest machine for a human genome, but we are the cheapest if you want to look at 200 genes or a pathogen behind an outbreak,” says Rothberg. He predicts that by 2013, Ion Torrent will have developed a chip capable of sequencing an entire human genome.

However, many of the most medically relevant tests that physicians want to run today encompass only tens or hundreds of genes. And in these cases, the biggest advantage of the new technology is its speed; it can sequence a sample of DNA in a couple of hours, rather than the week or more required by most of the machines now on the market. For genetic diagnostics, physicians want results fast. The Ion Torrent machine, however, is still considered a research device; it has not yet been approved by the U.S. Food and Drug Administration for clinical use.

Yemi Adesokan, cofounder of the genomics startup Pathogenica, is using Ion Torrent’s technology to develop a test for human papilloma virus in pap smear samples. Unlike existing tests, the Ion Torrent one will be able to detect infection with multiple strains of the virus, which can be linked to an increased risk of cancer. “It works really well, particularly in terms of turnaround time,” says Adesokan.

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